Impact of Total Protein and Triglycerides on the comparability of Sodium and Potassium Measurements by Direct and Indirect Ion-Selective Electrodes : An Experimental Analytical Study.

BACKGROUND: Electrolyte analysers use ion selective electrode (ISE) technologies, either 'direct'(dISE) or 'indirect'(iISE). Indirect methods are susceptible to errors in samples with high protein or lipid content. This study evaluated the individual and combined effects of elevated total proteins(TP) and triglycerides(TG) on sodium(Na+) and potassium(K+) measurements. METHODS: Fifty serum samples were pooled to prepare a low-protein, low-lipid matrix. Three enrichment series were generated using graded additions of 20% human albumin, 20% Intralipid, or both to achieve varying TP and TG. All samples were analysed for Na+ and K+ using dISE and iISE. The difference between methods (iISE-dISE) was correlated with TP and TG using regression and Bland-Altman analyses. A multivariable model assessed predictors of electrolyte bias. RESULTS: Albumin addition produced negative sodium bias, reaching upto 10% at TP>13g/dL, while potassium changes remained small. Triglycerides caused marked sodium underestimation at high levels (>2000 mg/dL) with minimal effect on potassium levels. When both interferents were elevated, sodium disagreement was high (bias -5.4mmol/L; limits of agreement -19.1 to +8.2), reflecting a strong cumulative effect. Multivariable regression showed TP as the strongest predictor of Na+ bias (R2 = 0.67), with minimal contribution by TG. CONCLUSION: This experimental study demonstrates that increasing concentrations of total protein and triglycerides, particularly when both are elevated produce significant negative biases in sodium measured by iISE, while potassium values remain comparable. These findings become clinically relevant in critical care/ cancer patients where they receive albumin and/or lipid infusions and dISE/iISE results are used interchangeably for patient monitoring.